Collective findings from clinical trials show that, for women with early-stage breast cancer who have a low 21-gene recurrence score, adding chemotherapy to standard hormonal therapy does not show a difference in survival, explained Kathy Albain, MD, a professor of Medicine at Loyola University Chicago Stritch School of Medicine.

For example, in the TAILORx trial,1 women with node-negative (N0), estrogen receptor (ER)–positive, HER2-negative breast cancer with a 21-gene recurrence score of less than 11 showed excellent invasive disease-free survival (iDFS), recurrence-free survival (RFS), and overall survival (OS) outcomes, despite the omission of adjuvant chemotherapy. For 1626 women with a low recurrence score in the trial, the iDFS rate at 5 years was 93.8% (95% CI, 98.7-99.6), the RFS rate at a distant site was 99.3% (95% CI, 98.7-99.6), and the OS rate was 98.0% (95% CI, 97.1-98.6).

An analysis of the SEER database published in Nature showed similar results.2 A group of 21,023 women with N0, hormone receptor (HR)–positive, HER2-negative breast cancer with a recurrence score below 18 showed a 0.4% risk of breast cancer-specific mortality at 5 years (95% CI, 0.3-0.6). A majority of these women did not receive chemotherapy. In patients with node–positive breast cancer, the risk of breast cancer-specific mortality was 1% at 5 years (n = 2694; 95% CI, 0.5-2.0).

“It’s clear that you can be very reassured even in recurrence scores under 18 in avoiding chemotherapy,” said Albain in a presentation during the 2016 International Congress on the Future of Breast Cancer.

The B-28 and B-14 trials found that ESR1 expression could be used in conjunction with the 21-gene recurrence score to further improve prognosis prediction.3 The recurrence score was capable of determining prognosis for both early and late outcomes when the ESR1 expression was high; however, only early outcomes were predicted when ESR1 expression was low.

The risk of recurrence in the low recurrence score group with low ESR1 expression (n = 66) was 9.1% for up to 5 years (95% CI, 14.2-19.2) and 17.6% for 5 to 10 years (n = 58; 95% CI, 9.9-30.3). The recurrence risk for the high ESR1 expression group (n = 320) was 8.3% for up to 5 years (95% CI, 5.7-11.9) and 10.5% for 5 to 10 years (n = 279; 95% CI, 7.3-14.8).3

The SWOG S8814 trial showed that the addition of chemotherapy to hormonal therapy did not improve survival.4 This trial studied tamoxifen with or without chemotherapy in patients with ER+ node–positive breast cancer. In patients with a recurrence score below 18, the 10-year breast cancer-specific survival rate for the tamoxifen group was 92% versus 87% for the group receiving tamoxifen plus cyclophosphamide, doxorubicin, and fluorouracil (stratified log-rank P = .56).

“The bottom line here [was that] low ESR metagene was significantly associated only with early recurrence but the high proliferation [was] significantly associated with early and late events,” Albain said, noting again the importance of the recurrence score.

For patients with node–positive early breast cancer, the question of whether or not genomic profiling should be used to guide adjuvant treatment decisions is controversial. Recent NCCN guidelines supported the use of the 21-gene recurrence score when deciding if patients should receive chemotherapy in combination with standard hormone therapy. Alternatively, ASCO’s recent biomarker guidelines say that no genomic profiling system should be used when deciding if chemotherapy should be added.

Albain personally agreed with the NCCN guidelines supported by outcomes from trials encompassing over 10,000 patients with node–positive disease across the world, which all show consistent results for recurrence score and similar genomic profiling methods in predicting outcomes for patients with early breast cancer.

“I think we should offer patients the option to forgo chemotherapy based on genomic profiling,” Albain said. “I’m coming down on the side of NCCN and others and against the ASCO guideline. I think the patients deserve to hear about the option.”